Clinical Management of Bleeding Risk With Antidepressants

Ann Pharmacother. 2019 Feb;53(2):186-194. doi: 10.1177/1060028018794005. Epub 2018 Aug 6.


Objective: This nonsystematic review describes risk of bleeding in treatment with serotonin reuptake inhibitors (SRIs) and provide recommendations for the management of patients at risk of bleeding.

Data sources: Articles were identified by English-language MEDLINE search published prior to June 2018 using the terms SRI, serotonin and noradrenaline reuptake inhibitors, OR antidepressive agents, AND hemorrhage OR stroke.

Study selection and data extraction: Meta-analyses were utilized to identify information regarding risk of bleeding with antidepressants. Individual studies were included if they had information regarding bleeding risk with specific SRIs, timing of risk, or risk with medications of interest.

Data synthesis: SRIs increase risk of bleeding by 1.16- to 2.36-fold. The risk is synergistic between SRIs and nonsteroidal anti-inflammatory drugs (NSAIDs; odds ratio [OR] range between studies 3.17-10.9). Acid-reducing medications may mitigate risk of gastrointestinal bleeds in chronic NSAIDs and SRI users (OR range between studies 0.98-1.1). Antidepressants with low or no affinity for the serotonin transporter, such as bupropion or mirtazapine, may be appropriate alternatives for patients at risk of bleeding. Relevance to Patient Care and Clinical Practice: This review includes data regarding bleeding risk for specific antidepressants, concomitant medications, and risk related to duration of SRI use. Considerations and evidence-based recommendations are provided for management of SRI users at high bleeding risk.

Conclusions: Clinicians must be aware of the risk of bleeding with SRI use, especially for patients taking NSAIDs. Patient education is prudent for those prescribed NSAIDs and SRIs concurrently.

Keywords: anticoagulation; antidepressants; antiplatelets; nonsteroidal anti-inflammatory drugs; proton pump inhibitors; serotonin.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects*
  • Bupropion / adverse effects
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Hemorrhage / therapy*
  • Humans
  • Mirtazapine / adverse effects
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Bupropion
  • Mirtazapine